硼替佐米对骨髓移植清髓照射小鼠肝及小肠内NF-κB表达的影响

摘要

目的 研究硼替佐米对骨髓移植照射预处理小鼠肝及小肠内NF-κB表达的影响,进一步探讨硼替佐米防治小鼠急性移植物抗宿主病(aGVHD)的作用机制.方法 骨髓移植预处理方法为BALB/c小鼠接受7.0 Gy X射线全身照射.实验分为:A组为空白对照组:未作任何处理;B组:单纯全身照射组;C组:全身照射加用硼替佐米组.观察各组小鼠的外周血白细胞计数及生存时间,Western blot法检测肝及小肠组织总蛋白及细胞核内NF-κB的表达.结论 B、C组中用于白细胞计数及生存时间观察的8只小鼠均在10 d内全部死于骨髓衰竭.照射后+1、+3、+5 d,B组肝及小肠组织总蛋白及细胞核蛋白中NF-κB p65表达均高于A组(P<0.05),而C组均明显低于B组(P<0.05).结论 硼替佐米可能通过一定程度上抑制照射预处理损伤所致肝脏及小肠组织中NF-κB的表达与激活,起到减轻aGVHD的作用.%Objective To investigate the mechanism of the preventive effect of bortezomib on graft -versus-host disease in mouse. Methods BALB/C mice were exposed to 7.0 X-ray irradiation. The experiments were designed as follows ;BALB/C mice received total body irradiation(TBI) by 7.0 Gy X radiation. The BALB/c mice were randomly into three groups :Group A was normal group ;Group B was irradiated along;Group C was recived TBI on day 0 and 0. 5 mg?kg-1 bortezomib of intravenous injection on days 0 and +3. The peripheral blood counts and survival time were observed in various group . The expression of NF-κB was detected by western blot. Results All mice in group B and C died of hematopoietic failures within 10 days after TBI. NF-κB p65 level in nucleus, total extracts of liver and small intestine in group B was significantly higher than that in group A on days 1,3 and 5 ( P < 0.05 ) . Furthermore, the nuclear and total NF-κB p65 proteins of liver and small intestine was increased more markedly in group B than group C ( P < 0. 05 ). Conclusion The underlying mechanism for Bortezomib to relieve aGVHD may be that it can inhibite the activation and expression of NF -κB.